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Biomedical subjects

R L Boyd

Publications and source records attributed to R L Boyd.

At least 37 records · Page 2Linked to original sources

Use of genetically manipulated strains of Clostridium perfringens reveals that both alpha-toxin and theta-toxin are required for vascular leukostasis to occur in experimental gas gangrene.

A hallmark of gas gangrene (clostridial myonecrosis) pathology is a paucity of leukocytes infiltrating the necrotic tissue. The cause of this paucity most likely relates to the observation of leukocyte aggregates at the border of the area of tissue necrosis, often within the microvasculature itself. Infecting mice with genetically manipulated strains of Clostridium perfringens type A (deficient in either alpha-toxin or theta-toxin production) resulted in significantly reduced leukocyte aggregation when alpha-toxin was absent and complete abrogation of leukocyte aggregation when theta-toxin was absent. Thus, both alpha-toxin and theta-toxin are necessary for the characteristic vascular leukostasis observed in clostridial myonecrosis.

Animals↗

Comparative efficacy of a rotary and a sonic powered toothbrush on improving gingival health in treated adult periodontitis patients.

PURPOSE: To compare the efficacy of two powered brushing instruments (Rota-dent, rotary action instrument and Sonicare, a sonic instrument) for reductions of plaque and gingivitis in a treated adult periodontal patient population. MATERIALS AND METHODS: Forty patients, randomly selected from a pool of patients in periodontal maintenance after surgical periodontal treatment, completed this study. A split mouth, blind, crossover design was utilized in this 12-week trial with each patient acting as his/her own control. After subjects alternately brushed one-half of their mouths with each of the instruments; a crossover in the brushing pattern occurred at 6 weeks, with no wash out period. Single-blind clinical assessments were made by a calibrated investigator at six sites per tooth for contralateral incisors, premolars and molars at baseline, 6 and 12 weeks. Gingival Index (GI), Plaque Index (PI) and Papillary Bleeding Index (PBI) were determined. A prophylaxis was done for all subjects after baseline recordings. RESULTS: Mean percent reductions from baseline for GI, PI and PBI at the end of 6 and 12 weeks were 75.0%, 68.9%, 73.4% and 76.4%, 69.9%, 74.0%, respectively for the rotary instrument, and 57.7%, 53.3%, 54.3% and 57.7%, 53.6%, 54.7%, respectively for the sonic brush. One-way ANOVA indicated that the rotary instrument was significantly more effective (P < 0.005) than the sonic brush in removing plaque and reducing gingivitis in treated adult periodontitis patients.

Adult↗

The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool.

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.

Animals↗

Etiology and sequelae of root resorption.

This article reviews the current status of investigation into apical root resorption within the context of orthodontic treatment. Treatment and patient factors that have traditionally been investigated are discussed, along with the results of current research in this area. The need for rethinking traditional research strategies in the quest for identifying both control and causative mechanisms is explored. Finally, proposals for key areas of future interest are highlighted.

Animals↗

Positive selection of low responsive, potentially autoreactive T cells induced by high avidity, non-deleting interactions.

Using a novel cell suspension model we investigated the relative abilities of nominal peptide and variants thereof to modulate de novo positive selection of lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic T cells. Confirming our earlier findings intermediate concentrations (10(-7) to 10(-5) M) of the nominal agonist peptide, p33, induced CD8 co-receptor down-modulation at the level of the entire receptor and the CD8beta chain as a consequence of high but non-deleting signal interactions. Agonist peptide variants caused down-modulation of the CD8beta chain but to a lesser degree. An antagonist peptide capable of inducing positive selection did not cause such modifications of the co-receptor. The positively selected TCRhiCD8alpha alpha and TCRhiCD8- cells were functional but not as efficient as TCRhiCD8alphabeta cells, presumably due to lower avidity interactions in the absence of the CD8beta chain or entire co-receptor. CD8beta mRNA was absent in these cells and was not up-regulated when further stimulated with fresh antigen-presenting cells pulsed with 10(-5) M p33. Effectively our data suggest that it is not the agonist or antagonist nature of a peptide per se but the overall strength of signalling that determines whether a cell will be positively or negatively selected, or die by neglect. Furthermore the agonist/antagonist properties of peptides defined at the level of mature T cell function do not unequivocally predict their effect on positive/negative selection. The ability of the T cell to down-modulate its CD8 co-receptor in response to high but non-deleting peptide interactions during positive selection allows the survival of T cells with a broader range of affinities and represents a possible mechanism by which low responsive but potentially autoreactive cells may escape into the periphery.

Acetyltransferases↗

An adult thymic stromal-cell suspension model for in vitro positive selection.

Presented here is a cell-suspension model for positive selection using thymocytes from alphabeta-TCR (H-2Db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (LCMV) on a nonselecting MHC background (H-2d or TAP-1 -/-), cocultured with freshly isolated adult thymus stromal cells of the selecting MHC type. The thymic stromal cells alone induced positive selection of functional CD4- CD8+ cells whose kinetics and efficiency were enhanced by nominal peptide. Fibroblasts expressing the selecting MHC alone did not induce positive selection; however, together with nonselecting stroma and nominal peptide, there was inefficient positive. These results suggest multiple signaling in positive selection with selection events able to occur on multiple-cell types. The ease with which this model can be manipulated should greatly facilitate the resolution of the mechanisms of positive selection in normal and pathological states.

Animals↗

Thymic-shared antigen-1 (TSA-1). A lymphostromal cell membrane Ly-6 superfamily molecule with a putative role in cellular adhesion.

The seeding and colonization of the thymus by bone marrow stem cells and the maturation of these cells into mature T lymphocytes are dependent on cell-surface recognition events between different cell lineages within the thymic microenvironment. Positive and negative selection processes within the thymus produce a peripheral T-cell repertoire capable of recognizing peptides derived from foreign antigen bound to self MHCmolecules. In addition to the TCR/MHC-peptide interaction, many other cell-surface molecules act in concert to regulate the kinetics of cellular interactions and intracellular signaling events during thymopoiesis. We have investigated the complexity of the thymic stroma by using monoclonal antibodies to clone cell-membrane molecules of thymic stromal cells. Thymic-shared antigen-1 (TSA-1) is a molecule of interest because it is expressed by both immature thymocytes and stromal cells. We report herein the structural and evolutionary relationships between TSA-1 and molecules of the Ly-6 superfamily (Ly-6SF), and present evidence that TSA-1 functions as a cell-surface receptor by binding a cognate cell target molecule on the surface of a subset of thymocytes.

Amino Acid Sequence↗

A comparative analysis of the murine thymic microenvironment in normal, autoimmune, and immunodeficiency states.

It is widely accepted that the thymic microenvironment regulates normal thymopoiesis through a highly coordinated and complex series of cellular and cytokine interactions. A direct corollary of this is that abnormalities within the microenvironment could be of etiologic significance in T-cell-based diseases. Our laboratory has developed a large panel of monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial markers in the thymus. We have taken advantage of these reagents to characterize the thymic microenvironment of several genetic strains of mice, including BALB/cJ, C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcphme/Hcphme, and ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control mice, including strains of several backgrounds, have a very consistent phenotypic profile with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix. In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex and medulla at both the structural and cellular levels. These phenotypic data suggest that abnormalities in interactions between developing thymocytes and stromal cells characterize disease-prone mice.

Animals↗

Clinical and laboratory evaluation of powered electric toothbrushes: in vivo determination of average force for use of manual and powered toothbrushes.

Mechanical oral hygiene instruments are intended to aid in the removal of stain and dental plaque from tooth surfaces. Certain home hygiene procedures, however, can lead to soft and hard tissue trauma. Power assisted brushing instruments are gaining in popularity, yet there is limited information on the interaction of these home care instruments with commercial dentifrices, and the resultant impact on oral tissues. In this study, the average forces applied during in vivo toothbrushing were determined for three powered brushing instruments (Rota-dent, Interplak and Braun Oral-B Plaque Remover) and a manual toothbrush (Oral-B P40). The Rota-dent instrument was found to be used with the lowest brushing pressure followed, in order, by the Braun Oral-B Plaque Remover. Interplak and the manual toothbrush. The average amount of dentifrice applied to the three powered brush heads was directly related to the size of the head, with Rota-dent typically receiving the least and Interplak the most applied dentifrice.

Adolescent↗

Clinical and laboratory evaluation of powered electric toothbrushes: laboratory determination of relative abrasion of three powered toothbrushes.

Previously established data on average forces applied to various brushing instruments during in vivo toothbrushing were incorporated into a laboratory abrasion model. The apparatus included a specially constructed and standardized brushing machine and utilized an acrylic resin substrate. Three powered brushing instruments (Rota-dent, Interplak and Braun Oral-B Plaque Remover) and a manual toothbrush (Oral-B P40), were compared in this model. The system demonstrated excellent precision and could distinguish between brushing instruments with as little as 10% difference in abrasivity. It was found that brushing abrasivity increased in the order of Rota-dent < Braun < Interplak.

Acrylic Resins↗

Clinical and laboratory evaluation of powered electric toothbrushes: laboratory determination of relative interproximal cleaning efficiency of four powered toothbrushes.

The clinical brushing data from the paper entitled, Clinical and Laboratory Evaluation of Powered Electric Toothbrushes: In Vivo Determination of Average Force for Use of Manual and Powered Toothbrushes, by Boyd et al. in this Special Issue, were incorporated into a laboratory cleaning model. Utilizing a standardized brushing machine and a methyl methacrylate substrate, four powered brushing instruments were tested for cleaning efficiency: Rota-dent. Braun Oral-B. Interplak and Sonicare, and a manual toothbrush (Oral-B P40). The Sonicare powered brushing instrument was tested at the manufacturer's recommended brushing force of 0.5 N as well as a calculated force of 1.0 N. The results showed that the Rota-dent was more efficient (p < 0.01-0.001) in removing stain from both flat and interproximal surfaces than any of the other tested brushes. These results, together with those reported by McLey, et al. in Clinical and laboratory Evaluation of Powered Electric Toothbrushes: Laboratory Determination of Relative Abrasion of Three Powered Toothbrushes in this Special Issue, demonstrate that the rotary action Rota-dent instrument has the most efficient combination of low abrasion and high cleaning efficiency of the four powered brushes and the manual brush when all instruments were tested using clinically documented pressures.

Analysis of Variance↗

Clinical and laboratory evaluation of powered electric toothbrushes: relative degree of bristle end-rounding.

Toothbrush bristles with sharp edges have been postulated to represent a greater threat to dental tissues than end-rounded bristles. This study evaluated the effect of both in vivo and laboratory use on bristle wear rate, tip geometry and in vitro abrasivity. Three soft manual brushes (Oral-B P40, Crest Complete and Butler GUM) and one powered brush (Rota-dent) were tested. The results of this study show that the wear rate varied directly with brushing load and amount of dentifrice, and inversely with bristle diameter. Despite the initial geometry, a flat tip with rounded rims was typically observed after only 30 minutes of manual or Rota-dent brush use. There was no statistical difference in in vitro abrasion for new brushes versus used brushes.

Dentifrices↗

The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors.

The nude mutation (nu) causes athymia and hairlessness, but the molecular mechanisms by which it acts have not been determined. To address the role of nu in thymogenesis, we investigated whether all or part of the nude thymic epithelium could be rescued by the presence of wild-type cells in nude <--> wild-type chimeric mice. Detailed immunohistochemical analyses revealed that nude-derived cells could persist in the chimeric thymus but could not contribute to cortical or medullary epithelial networks. Nude-derived cells, present in few clusters in the medulla, expressed markers of a rare subpopulation of adult medullary epithelium. The thymic epithelial rudiment of nude mice strongly expressed these same markers, which may therefore define committed immature thymic epithelial precursor cells. To our knowledge, these data provide the first evidence that the nu gene product acts cell-autonomously and is necessary for the development of all major subpopulations of mature thymic epithelium. We propose that nu acts to regulate growth and/or differentiation, but not determination, of thymic epithelial progenitors.

Animals↗

Identification and functional analysis of Ly-6A/E as a thymic and bone marrow stromal antigen.

We recently described an mAb (MTS23) reactive with a membrane Ag expressed on a subset of thymic medullary stromal cells. This Ag is also constitutively expressed at high levels on peripheral B cells, macrophages, and thymic and splenic dendritic cells of C57BL/6 mice. A number of stromal cell lines derived from thymus and bone marrow also stain with MTS23, but thymocytes and peripheral T cells only weakly express the Ag detected by MTS23. Here we show that the molecule detected by MTS23 is a member of the Ly-6 family of phosphatidylinositol-anchored membrane proteins. Treatment of stromal cells with phosphatidylinositol-phospholipase C before staining completely abolished expression. Using transient expression of 293T cells and a cDNA library of a stromal cell line cloned into the pEF-BOS vector, a cDNA encoding the MTS23-target Ag was isolated. Partial sequencing and restriction enzyme mapping revealed that it represents the Ly-6A/E protein. While the physiologic significance of the presence of Ly-6 molecules on stromal cells is not clear, it has been known for some time that, at least in lymphocytes, cellular activation events can be induced upon Ly-6 engagement. We now demonstrate that Ly-6 also functions as a signal transduction molecule on stromal cells, in that granulocyte-macrophage CSF can be produced by a variety of stromal cell lines upon mAb-mediated cross-linking of Ly-6. Together with the dramatic up-regulation of Ly-6 expression on stromal cells upon IFN-gamma treatment, this is the first indication of a biologic function of an Ly-6 gene product on nonhemopoietic cells. The results suggest that Ly-6 may play a role in the cross-talk between lymphocyte precursors and stromal cells.

Animals↗